Sodium hydride → Tert-butyl 4-[(4-bromophenyl)methyl]-3-oxopiperazine-1-carboxylate

HRID 2366868Notes

Reaction equation

HRID 2366868 reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24]Br)=[CH:20][CH:19]=1>CN(C)C=O>[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:7]2[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][C:2]2=[O:1])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 685274-Bromobenzyl bromideHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 67196654Tert-butyl 4-[(4-bromophenyl)methyl]-3-oxopiperazine-1-carboxylateYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1,1-dimethylethyl 3-oxo-1-piperazinecarboxylate (500 mg, 2.497 mmol) in N,N-dimethylformamide (DMF) (8 mL) at room temperature under nitrogen was added sodium hydride (60% w/w in mineral oil, 120 mg, 3.00 mmol) and the resulting suspension was stirred at this temperature for 30 min. 1-Bromo-4-(bromomethyl)benzene (749 mg, 3.00 mmol) in DMF (5 mL) was then added via syringe. The resulting mixture was stirred at room temperature for 1.5 h then partitioned between AcOEt and water. The layers were separated and the aqueous phase was extracted three times with AcOEt. The combined organic phases were washed three times with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge (gradient: 13 to 63% AcOEt in Hexanes) gave 1,1-dimethylethyl 4-[(4-bromophenyl)methyl]-3-oxo-1-piperazinecarboxylate (763 mg, 2.066 mmol, 83% yield) as an oil which solidified to a white solid over 16 h.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 1.5 h
  2. customthen partitioned between AcOEt and water
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted three times with AcOEt
  5. washThe combined organic phases were washed three times with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-a3a590408d574f6baf876489fb64bf46
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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